1, 1, 2-tris-aryl-3-tertiary-amino-1-propenes, intermediates, and preparation thereof



1,1,2 TRIS ARYL 3 TERTIARY AMINO 1 PROPENES, INTERMEDIATES, AND PREPARA-TION THEREOF Bill Elpern, Walnut Creek, Califl, assignor to SterlingDrug Inc, New York, N.Y., a corporation of Delaware No Drawing. FiledFeb. 5, 1957, Ser. No. 638,200

15 Claims. (Cl. 260-293) 'This invention relates to amino substitutedtriphenylethylene derivatives, and is particularly concerned withl,1,2-tris-aryl-3tertiary-amino-l-propenes, salts thereof, and with aprocess for their preparation. The invention also relates tointermediates useful in the preparation of said propenes.

Among the compounds included within the scope of my invention are thosehaving the formula wherein R and R represent hydrogen, lower-alkyl,loweralkoxy, lower-alkylmercapto or halogen radicals, R. representshydrogen, lower-alkyl, lower-alkoxy or loweralkylmercapto radicals, andN=B represents a basic, aliphatic-type, tertiary-amino radical.

When R, R and R" in the above general Formula I represent loWer-alkyl,lower-alkoxy or lower-alkylmercapto radicals, they preferably containfrom one to about four carbon atoms, and thus represent such specificradicals as methyl, ethyl, propyl, isopropyl, butyl, isobutyl,tertiary-butyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy,methylmercapto, ethylmercapto, propylmercapto, isopropylmercapto,butylmercapto, isobutylmercapto, and the like. When R and R representhalogen they stand for any of the four halogens, fluorine, chlorine,bromine or iodine. In any given compound, R, R and R" can'be the same ordifferent and can be in any of the available positions in the benzenering.

In the above general Formula I, N=B represents a basic, aliphatic-type,tertiary-amino radical. These tertiary-amines are sufficiently basic toform readily acidaddition salts with inorganic or organic acids, and areof the type N(Y) (Y) wherein Y and Y are aliphatic substituents such asloWer-alkyl, cycloalkyl, alkenyl and the like or Where Y and Y arejoined to form a nonaromatic type heterocyclic ring. A preferred groupof N=B includes the radicals di-lower-alkylamino, l-piperidyl,l-pyrrolidyl, and 4-morpholinyl, and loWer-alkylated derivatives of saidl-piperidyl, l-pyrrolidyl and 4-morpholinyl radicals. In thedi-lower-alkylamino radicals the lower-alkyl radicals can have from oneto about six carbo atoms and can be the same or difierent.

The compounds of my invention are preparedaccording to the followingreaction scheme:

CHQ N =13 III 3,ill,%5 Patented Nov. 28, 1961 either in the free baseform or acid-addition salt form, and a1,2-bis-aryl-3tertiary-amino-l-propanone (III) is thus obtained. Thereaction is carried out under conditions commonly used for the Mannichreaction, e.g., in the presence of an inert reaction medium at atemperature between about 50 C. and 150 C. Some of the.

amino ketones of Formula III are disclosed and claimed in my copendingapplication, Serial No. 638,430, filed February 6, 1957.

The amino ketone (III) is then reacted with a Grignard reagent, RC HMgX, wherein X is halogen selected from chlorine, bromine and iodine,andthe resulting inter mediate complex is hydrolyzed to produce an aminocarbinol of Formula IV. The Grignard reaction is carried out in an inertreaction medium at a temperature between 0 C. and 150 C.

The amino carbinol (IV), either in the free base form or acid-additionor quaternary ammonium salt form, is dehydrated by contacting it withdehydrating agents to produce a compound of Formula I. The dehydratingagents are generally of an acidic nature and can be mineral acids,suchas hydrochloric, sulfuric or phosphoric acid; organic acids, such asformic acid, acetic acid, oxalic acid, or p-toluenesulfonic acid; saltssuch as potassium hydrogen sulfate or zinc chloride; or anhydrides, suchas phosphorus pentoxide or acetic anhydride. Heat may be applied ifdesired to speed up the reaction, although in some cases the dehydrationtakes place readily at room temperature.

The compoundsof the invention are most conveniently used in the form ofwater-soluble, non-toxic acid-addition and quaternary ammonium salts.Non-toxic salts are therapeutically acceptable salts whose anions arerelatively innocuous to animal organisms in therapeutic doses of thesalts, so that the beneficial physiological properties inherent in thefree bases are not vitiated by side-effects ascribable to the anions; inother words, the latter do not substantially increase the toxicityinherent in the cations. Appropriate acid-addition salts are thosederived from mineral acids such as hydrochloric acid, hydrobromic acid,hydriodic acid, nitric acid, sulfuric acid, and phosphoric acid; andorganic acids such as acetic acid, 'citric acid,

- lactic acid, tartar acid, ethanesulfonic acid, and quinic acid.

Thequaternary ammonium salts are obtained by the addition of esters ofstrong acids to the freebase form of the compounds. A preferred class ofesters comprises alkyl, alkenyl, and aralkyl esters of strong inorganicacids or organic sulfonic acids, including such compounds as methylchloride, methyl bromide, methyl iodide, ethyl bromide, propyl chloride,allyl chloride, allyl bromide, I

methyl sulfate, methyl benzenesulfonate, methyl p-toluenesulfonate,benzyl chloride, benzyl bromide, and substituted benzyl halides, such asp-chlorobenzyl chloride, p-nitrobenzyl chloride, p-methoxybenzylchloride, o-chlorobenzyl chloride, and the like. v

The acid-addition salts are prepared either by dissolving the free basein an aqueous solution containing the appropriate acid, and isolatingthe salt by evaporating the solution, or by reacting the free base andacid in an organic solvent, in which case the salt separates directly orcan be obtained by concentration of the solution.

The quaternary ammonium salts are prepared by mixing the free base andester of a strong acid in an inert solvent. Heating may be used tofacilitate the reaction, although salt formation usually takes placereadily at room temperature. The quaternary ammonium salt separatesdirectly or can be obtained by concentration of the solution.

It is also possible to convert one quaternary ammonium salt to anotherin which the anion is diflerent. If the anion of the original quaternarysalt forms a water-insoluble silver salt, the quaternary salt will reactwith silver oxide in aqueous medium to form the corresponding quaternalyammonium hydroxide, the original anion being removed as a precipitate.The quaternary ammonium hydroxide solution can then be neutralized withany desired acid, weak or strong, to produce a new quaternary ammoniumsalt in which the anion is difierent from that of the original salt. Inthis way quaternary ammonium salts in which the anion is derived from aweak acid can be obtained.

The invention also contemplates the intermediate 1,1,2-

ttissubstituted-aryl-3-(tertiary-amino)-l-propanols having the generalFormula IV, wherein R and R represent lower-al-koxy,iower-alkylrnercapto or halogen radicals, and R" represents lower-alkoxyor lower-alkylmercapto radicals, and acid-addition and quaternaryammonium salts thereof. The invention also relates to the preparat-ionof these intermediates by the reaction of a1,2-bissubstituted-aryl-3(tertiary-amino)-1-propanone of Formula IIIwith a substituted-phenylmagnesium halide and hydrolyzing theintermediate complex. The structures of the compounds of the inventionare established by the anode of their preparation and by chemicalanalysis. The structures of the compounds of Formula I are furtherconfirmed by ultraviolet and infrared spectra, which demonstrate thepresence of a stilbene structure.

The following examples will further illustrate the invention withoutlimiting the same thereto.

EXAMPLE 1 (a) 1 ,2-bis(4-methoxyphenyl) -3-dimethylamin0-1 propanone 100m1; of 35% sodium hydroxide solution, The product ethoxydesoxybenzoin,p-methoxyphenyl p-ethoxy-benzyl ketone, p-chlorophenyl m-methylbenzylketone, or 4,4- bis (methylmercapto)desoxybenzoin, there can beobtained, respectively,1,2-bis(4-ethoxyphenyl)-3-dlmethylamino-l-propanone [111; R, R are 4-C HO, N=B is N(CH l-(4-methoxyphenyl) 2 (4 ethoxyphenyD-B-dimethylamino-l-propanone EHI; R is 4-CH O, R is 4-C H O, N=B is N(CH1-(4-chlorophenyl)-2-(.3- methylphenyl)-3-dimethylamino-l-propanone[111; R is 4-Cl, R is 3-CH N=B is N(CH or 1,2-bis(4-methylmercaptophenyl)-3-dimethylamino 1 propanone [:III; R, R' are 4-CHS, N:B is N(CH By replacement of the dimethylamine hydrochloride in thepreceding preparation by a molar equivalent amount of diethylaminehydrochloride, dipropylarnine hydrochloride, methylethylaminehydrochloride, dibutylamine hy- V drochloride, dihexylaminehydrochloride, piperidine hywhich hadseparated after cooling in therefrigerator for about fifteen hours was collected by filtration anddried, I

giving 70.7 g. of 1,2-bis(4 methoxyphenyl)-3-dirnethylaminml-propanonke,M.P. 4748 C.

" The hydrochloride .salt of l,2-bis(4-.methoxyphenyl)- 3dimethylamino-l-propanone, prepared by the addition 1 of excess 10%alcoholic hydrogen chloride to a sample I of the free base dissolved inabsolute ethanol, had the M1. l6'6.5 '-l-67.5- C. (corn); whenrecrystallized from 1 an ethanol-'et-her'mixture."

" AnalySis-Calcd. for C H NO HCl:

0, 6523,15, 6592,01, 10.14. 'Found: C, 65.04; H, 6.83; CI, 1004.

By replacement of the desoxyanisoin "in the. precedingpre'p'aration'byfa molar equivalent atnount of 4,4-dimethylamino-l-propanone in thepreceding preparation 'panol, in the form of a dark red oil.

drochloride, pyrrol-idine hydrochloride, morpholine hydrochloride, orZ-methylpiperidine hydrochloride, there can be obtained, respectively,l,2-bis(4-methoxyphenyl)- 3-diethylamino-l-propanone Elli; R, R are 4-CHO, N=B is N(C H l,2-bis(4-methoxyphenyl)-3-dipropylamino-l-propanone[111; R, R are 4-CH O, N=B is N(C H-;) l,2-bis(4 methoxyphenyl) 3methylethylamino-l-propanone EIH; R, R are 4-CH O, N=B is N(CH (C H ll,2bis(4-methoxyphenyl) 3 dibutylarnino-l-propanone [111; R, R are 4-CHO, N=B is N(C ,H 1,2 bis(4 methoxyphenyl) 3 dihexylamino-l-propanone[111; R, R are 4-CH O, N=B is N(C H 1,2 bis( 4methoxyphenyl)-3-(1-piperidyl)- l-propanone UH; R, R are 4-CH O, N=B isNC H 1,2 bis'(4 methoxyphenyl) 3 (1 pyrrolidyl) 1- propanone [111; R, Rare 4-CH O, N=B is NC H 1,2 'bis(4 methoxyphenyl) 3 (4 moipholinyl) 1propanone [111; R, R are 4-CH O, N==B is NC H O], or1,2-bis(4-methoxyphenyl)-3-(2-methyl-1-piperidyl)-lpropanone [111; .R, Rare 4-CH O, N=B is NC H (CH 1 b) 1,1,2-tris(4-meth0xyphenyl)-3-dimethylamin0-1- .propanol A solution of4arnet-hoxyphenylmagnesium bromide [prepared from 56.1 g. (0.3 mole) of4-bromoanisole and 7.2 g. (0.3 mole) of magnesium in 250 ml. of dryether] was treated at 0 C. with a solution of 31.3 g. (0.1 mole) of1,2-bis(4-methoxyphenyl)-3-dimethylamino-l-propanone in 400 ml. oftoluene. The ether was removed by distillation, and the remainingmixture was refluxed (internal temperature 108 C.) for three hours.After standing at room temperature for about fifteen hours, the mixturewas hydrolyzed'by pouring it into 1 liter of ice water containing 275 g.of ammonium chloride. The organic layer was separated, the aqueous layerextracted with three 75 m1. portions of benzene, and the combinedorganic solutionswashed twice with water. The solvent was removed invacuo, the residue triturated with. absolute alcohol and filtered. Thealcoholic filtrate was concentrated in vacuo, giving 63.5 g. of1,1,2-tris(4-methoxyphenyl)-3-dimethylamino 1 pro- 0 The methiodide of1,1,2-tris(4-methoxyphenyl)-3-dimethylamino-lapropanol, prepared byheating a portion of the free base in benzene solution with an excess ofmethyl iodide, had the M.P.- 194,5-197" C, (c0rr.) when recrystallizedtwice from an ethyl acetate-methanol mixture.

Anal'ysisf-Calcd. :Eor C2qH34INO4: C, 57,57; H, 6.08; I, 22.52. Found:C, 57.30; H, 6.20; I, 22.08.

By. replacement of the l,2-bis(4-methoxypheny1) -3-diby a molarequivalent amount of 1,2-bis(4-ethoxyphenyl)-B-dimethylamino-l-propanone, .1 (4-methoxyphenyD-2-(4-ethoxyph'eny1)-3-dirnethylamino 1 propanone, 1-(4- chlorophenyl)-2-(3-methylphenyl) 3 dimethylamino-1 propanone,1,2-bis(4-methy1mercaptophenyl)-3-dimethylamino-l-propanone,1,2-bis(4methoxyphenyl)-3-diethylamino-l-propanone, 1,2bis(4-methoxyphenyl)-3-dipropylaminol-propanone,1,2-bis(4-methoxyphenyl) -3-methylethylamino 1 propanone, 1,2 bis(4methoxyphenyl) 3 dibutylamino 1 propanone, 1,2 bis(4-methoxyphenyl)-3-dihexylamino-1-propanone, 1,2-bis(4- methoxyphenyl) -3-l-piperidyl) -1-propanone, 1,2-bis(4- methoxyphenyl)-3-( l-pyrrolidyl)-l-propanone, 1,2-bis (4- methoxyphenyl)-3-(4-morpholinyl)-1-propanone,or 1,2- bis(4-methoxyphenyl)-3-(Z-methyl-l-piperidyl) 1 propanone, therecan be obtained, respectively, 1,2-bis(4- ethoxyphcnyl -1-(4-methoxyphenyl) -3 -dimethy1amino 1- propanol [IV; R, R are 4-C H O, R"is 4-CH O, N=B is N( CH l,2-bis(4-methoxyphenyl -2-4-ethoxyphenyl)-3-dimethylamino-1-propanol [IV; R, R are 4-CH O, R is4-C H O, N=B is N (CH 1-(4-chlorophenyl)-l- (4methoxyphenyl)-2-(3-methylphenyl)-3-dimethylamino-l-propanol [IV; R is4-Cl, R is 3-CH R" is 4-CH O, N=B is N(CH1,2-bis(4-methy1mercaptophenyl)-1-(4-methoxyphenyl)-3-dimethylamino-1-propanol [IV; R, R are 4-CH S, R" is4-CH O, N=B is N(CH 1,1,2-tris(4-methoxyphenyl)-3-diethylamino-1-propanol [IV; R,

methoxyphenyl)-3-dipropylamino-l-propanol [IV; R, R, R" are 4-CH O, N=Bis N(C3H7)2], 1,1,2-tris(4-methoxyphenyl)-3-methylethy1amino-l-propanol[IV; R, R, R are 4-CH 0, N=B is N(CH )(C H 1,1,2-tris(4-methoxyphenyl)-3-dibutylamino-1-propanol [IV; R, R, R are 4-CH O, N=B isN(C H 1,1,2-tris(4-methoxyphenyl)-3-dihexylamino-l-propanol [IV; R, R,R" are 4-CH O, N=B is N(C H1,1,2-tris(4-meth0xyphenyl)-3-(1-piperidyl)-1-propanol [IV; R, R, R are4-CH O, N=B is NC H 1,1,2-tris(4-methoxyphenyl)-3-(1-pyrrolidyl)-1-propanol [IV; R, R, R" are 4-CH 0, N=B is NC Hl,1,2-tris(4-methoxyphenyl)-3-(4-morpholinyD-l-propanol [IV; R, R', R"are 4-CH O, N=B is N'C H O], or 1,l,2-tris(4-methoxyphenyl)-3-(2-methy1-1-piperidyl)-1-propanol [IV; R, R, R" are 4-CH O, N=B is NC5H9(CH3)].

(c) 1,1,2-tris(4-meth0xyphenyl) -3-dimethylamino-1- propene A solutionof 10.8 g. of 1,1,2-tris(4-meth0xyphenyl)- 3-dimethylamino-l-propanol in50 ml. of absolute ethanol was saturated with hydrogen chloride gas. Thesolution was concentrated, and the residue was dried by adding ethylacetate and benzene and again concentrating the solution. The residuewas crystallized from an ethyl acetate-ether mixture and thenrecrystallized from abs0-' acid, methyl iodide, ethyl bromide, or benzylchloride,

to give, respectively, the hydrobrornide, quinate, ethanesulfonate,methiodide, ethobromide, or benzochloride salts of 1,1,2 tris(4-methoxyphenyl)-3-dimethy1amino-1-propene.

By replacement of the 1,1,2-tris(4-methoxyphenyD-3-dimethylamino-lrpropanol in thepreceding preparation by a molarequivalent amount of 1,2-bis(4-eth0xyphenyl)- phenyl)-3-dipropylamino-1-propano1,1,1,2-tris(4-methoxyphenyl)-3-methylethylamino 1 propanol, 1,1,2-tris(4-methoxyphenyl)-3-dibutylamino-l-propanol, 1,l,2-tris(4- methoxyphenyl-3-dihexylaminol-propanol, 1, 1,2-tris (4- methoxyphenyl) -3-(l-piperidyl) -l-propanol, 1,1,2-tris(4- methoxyphenyl) -3-(1-pyrro1idyl)-1-propanol, 1,1,2-tris(4-methoxyphenyl)-3-(4-morpholinyl)-1-propanol, or 1,1,2-tris(4-methoxyphenyl)-3-(2-methyl-1-piperidyl) l propanol, there can beobtained, respectively, 1,2bis(4-ethoxyphenyl)-1-(4-methoxyphenyl) 3dimethylamino-lpropene [1; R, R are 4-C H O, R" is 4CH O, N=B is N(CH1,2-bis(4-methoxyphenyl)-2-(4 ethoxyphenyl)-3-dimethylamino-l-propene[I; R, R are 4-CH O, R is 4-C H O, N=B is N(CH 1-(4-chlorophenyl)-l-(4-methoxyphenyl)-2-(3-methylphenyl) 3 dimethylamino-l-propene [1; R is4-Cl, R is 3-CH R" is 4-CH O, N=B is N(CH1,2-bis(4-methylmercaptophenyl)-1-(4-methoxypheny1)-3-dimethy1amino-l-propene [I; R, R are 4-CH S, R is4-CH O, N=B is N(CH 1,1,2-tn's(4-methoxyphenyl)-3-diethylamino-1-propene [I; R, R, R" are 4-CH O, N=Bis N(C H l,1,2-tris(4-methoxyphenyl)-3-dipropylamino-l-propene [1; R, R,R" are 4-CH O, N=B is N(C H1,1,2-tris(4-methoxyphenyl)-1-methylethylamino-l-propene [-I; R, R," R'are 4-CH O, N=B is N(CH (C H1,1,2-t1'is(4-meth0xyphenyl)-3-dibutylamino-l-propene [1; R, R, R" are4-CH O, N=B is N(C.,H1,1,2-tris(4-methoxyphenyl)-3-dihexylamino-l-propene [1; R, R, R are4-CH O, N=B is N(C H 1,1,2-tris(4-methoxyphenyl)-3-(lpiperidyD-l-propene [1; R, R, R are 4-CH O, N=B is NC H1,1,2-tris(4-methoxyphenyl) -3-( l-pyrrolidyD-lpropene [I; R, R, R are4-CH O, N=B is NC H1,1,2-tris(4-methoxyphenyl)-3-(4-morpholinyl)-l-propene [I; R, R, R are4-CH O, N=B is NC H O], or 1,1,2-tris(4-methoxyphenyl)-3-(2-methyl-1-piperidyl) 1 propene [1; R, R, R are4-CH O, N=B is NC H (CH EXAMPLE 2 (a) 1,2-diphenyl-3-(l-piperidyl)l-propanone [III; R, R are H, N=B is NC H was prepared from 29.4 g.(0.15 mole) of desoxybenzoin, 19.5 g. (0.16 mole) of piperidinehydrochloride and 11.2 g. (0.335 mole) of paraformaldehyde according tothe manipulative procedure described above in Example 1, part (a). Thehydrochloride saltof the product did not crystallize from the reactionmixture, so the solvent was removed in vacuo and the residue stirredwith ice and sodium hydroxide solution to convert the product to thefree base. There was thus obtained 77.6 g. of 1,2-diphenyl-3dimethylarnino-l-propanone, M.P. 8890 C. when recrystallized fromethanol.

1-(4 methoxyphenyl)-3-dimethylamino-1propanol, 1,2-

bis(4-methoxyphenyl)-2-(4-ethoxyphenyl). 3 dimethylamino-l-propanol,1-(4-chlorophenyl) 1(4-methoxyphenyl)-2-(3-methylphenyl)-3-dimethylamino 1 propanol, 1,2-bis(4-methylmercaptopheuyl) -1- (4-methoxyphen- Analysis.-Ca1cd. for C HN0: C, 81.86; H, 7.90; N, 4.78. Found:-C, 81.94; H, 7.83; N, 4.76.

(b) l,1,2-tripheny1-3-(lpiperidyl)-l-propanol [IV; R, R, R" are H, N=Bis NC H l was prepared from 7.3 g. (0.3 mole) ofrnagnesium, 47.2 g. ofbromobenz'ene and 29.3 g. (0.1 mole) of l,2-diphenyl-3-(1-piperidyl)'-1-propanone according to the manipulative proceduredescribed above in Example 1, part (b). There was thus obtained1,1,2-triphenyl-3-(l-piperidyl) 1 propanol, M.P. 170- 170.5 C.

Analysis-Calm. for C H NO: N, 3.77. Found: N, 3.66.

(c) 1,1,2-triphenyl-3-(1 -piperidyl) -pr0pene 1; R, R, R are H, N=B isNC H A mixture of 2 g. (0.0054 mole) of 1,1,2-triphenyl-3-(l-piperidyl)-l-propanol and 1.5 g. (0.0087 mole) of p-toluenesulfonicacid was stirred for three hours at -125 C. The reaction mixture wascooled, 20 ml. of absolute ethanol was added, the mixture warmed toeifect solution and then cooled in an ice bath. The proda 7 v. not whichseparated was collected by filtration, washed with ether and driedvat 750., giving 1,1,2-triphenyl-3 f(1-piperidyl)-1 propene in the form of itsp-toluenesulsalt forms has shown that they are useful as cardiacantiaccelerators and coronary dilators. They possess a mode of actionsomewhat similar to that of veratramine and thus are useful in treatmentof hypertensive states. The compounds of the invention are, however,much less toxic than veratramine; for example,l,l,2-tris(4-methoxyphenyl)-3-dimethylamino-l-propene was found to havean intravenous LD value in mice of 30:1 nag/kg, and an oral LD value of385x85 mg./kg.', whereas the values for veratramine are 3.68:0.24nag/kg. and 13:21 mg./kg., respectively. 1,1,2 tris(4methoxyphenyl)-3-dimethylamino-l-propene had an approximate effectivedose (AED5Q) of 31 micrograms per heart as a cardiac decelerator whenmeasured upon'the isolated rabbit heartand a coronary dilator activityof 2-2.6 times that of papaverine when measured upon the isolated,perfused rabbit heart. The compounds can be administered orally astablets or capsules compounded with conventional excipients, orparenterally or intravenously as aqueous solutions.

I claim: 1 I

I 1. Compounds selected from the group consisting of (A) compoundshaving the formula l CHr-N=B wherein R and 'R represent a member of thegroup consisting of hydrogen, lower-alkyl, lower-alkoxy,"loweralkyhnercapto and halogen, R" represents a member of the groupconsisting of hydrogen, lower-alkyl, loweralkoxy andlower-alkylmercapto, and N=B represents nary ammonium salts thereof.

'2. Pharmacologically acceptable,acid-addition salts of compounds havingthe formula .i 7 o=os v Q ina-N n I I a" V V j V wherein ,R, R and R"represent lower-alkoxy and N=B represents di-lower-alkylamino.

3. Compounds having the formula wherein R, R and R". representlower-alkox'y and N=B represents di-lower-alkylamino.

4. Pharmacologically acceptable acid-addition salts of 1,1,2 tris(4methoxyphenyl) 3 dimethylamino 1- propene.

5 l, 1 ,Z-tris (4-methoxyphenyl) -3-dimethylamino-1-propene.

6. l,1,2-tris (4-methoxyphenyl)-3-dimethylamino-1-propene-hydrochloride.

7. 1, 1,2-triphenyl-3- l-piperidyl) l-propene.

I 8. Pharmacologically acceptable acid-addition salts of 1,1,2-triphenyl-3- l-piperidyl -1-propene.

' 9. 1,1,2-triphenyl-3-(l-piperidyl-l-propene hydrochlo- 'ride.

10. l,1,2-tripheny1-3 -(l-piperidylyl-propene p-toluenesulfonate.

11. The process for preparing a compound having the formula V a R 13 1CH:N=B

wherein R and R represent a member of the group con- 0H=N=B with adehydrating agent. r g

12. The process for preparing a compound having the formula wherein R, RR represent lower-alkoxy and N=b represents diJOwer-alkylamino, whichcomprises contacting a compound having the formula :CHfN= B with anacidic dehydrating agent.

13. The process for preparing1,1,2-tris(4-methoxyphenyl)-3-dimethy1amino-1-propene which comprisescontacting 1,1,2-tris(4-methoxyphenyl)-3-d.imethylamino-lpropanol Withan acidic dehydrating agent.

14. The process for preparing 1,1,2-triphenyl-3-(l-piperidyl)-1-propenewhich comprises contacting 1,1,2-triphenyl-B-(l-piperidyl)-1-propanolwith an acidic dehydrating agent.

15. The process for preparing a compound having the formula wherein Rand R represent a member of the group consisting of hydrogen,loWer-alkyl, lower-alkoxy, loweralkylmercapto and halogen, R" representsa member of the group consisting of hydrogen, lower-alkyl, loweralkoxyand loWer-alkylmercapto, and N=B represents a member of the groupconsisting of di-lower-alkylamino, l-piperidyl, l-pyrrolidyl,4-morpho1inyl, lower-alkylated l-piperidyl, lower-alkylatedl-pyrrolidyl, and lower-alkylated 4-morpholinyl, which comprisesreacting an acidic compound having the formula with a compound havingthe formula R"C H Mg-halide, hydrolyzing the intermediate complex, andcontacting the resulting compound having the formula with an acidicdehydrating agent.

References Cited in the file of this patent UNITED STATES PATENTS UNITEDSTATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3 010 965November 28,, 1961 Bill Elpern It is hereby certified that error appearsin the above numbered patent requiring correction and that the saidLetters Patent should read as corrected below.

Column 2 line 59 for 'tartar" read tartaric -3 column 6 line 26 for'lmethylethylamino" read -3-methyl ethylaminocolumn 8 line 22 for(lpiperidyl l-propene" read (l-piperidyl)lpropene" line 44 for anacidic" read a line 54 i for a dehydrating read an acidic dehydratingcolumn 10,, line l for an acidic read a Signed and sealed this 1st dayof May 1962o (SEAL) Attest:

ERNEST W SWIDER DAVID L. LADD Attesting Officer Commissioner of Patents

1. COMPOUNDS SELECTED FROM THE GROUP CONSISTING OF (A) COMPOUNDS HAVINGTHE FORMULA